Many commercially important polypeptides are recombinantly produced in cells that are adapted grown in culture. One of the limits to growing cell lines in culture is the decreased viability of the cells over time, which is partially rectified by the addition of growth factors. However, while this extra step improves cell viability, it adds significant costs to the production of the desired recombinant polypeptide.
Betaine has been shown to counteract the effects of hyperosmotic conditions in cell cultures in vitro, and also counteracts the denaturing tendency of urea (Kim et al., (2000) Biotechnol. Prog., 16:775–781; Ryu et al., (2000) Biotech. Bioeng., 70:167–175). However, it was also reported that betaine had no effect on cell culture growth or maximum viable cell concentration when cultures were at physiological ranges, i.e., 292 mOsm/kg, of osmolality (Ryu et al., (2000) Biotech. Bioeng., 70:167–175).
Thus, there is a need in the art for methods of improving the cell viability of cell cultures so as to reduce cell death, to reduce the dependence on growth factors to increase recombinant polypeptide production while not increasing costs. The invention fulfills this need by providing a simple, easy and inexpensive way of increasing cell viability and reducing the requirement for growth factors by cultured cells.